Human skin is the largest organ in the body and is made up of multiple layers of ectodermal tissue. Skin regulates temperature and serves as a barrier against foreign agents, toxic substances, microorganisms, pathogens, and injury guarding the underlying muscles, bones, ligaments and internal organs. Human skin varies in thickness from location to location and can be as thin as 0.5 mm on the eyelids and as thick as 4 mm in the soles, palms and scalp. The skin is composed of two primary layers, the epidermis and the dermis. As shown in FIG. 1, the epidermis includes the outermost layers of the skin and forms a protective barrier responsible for keeping water and essential elements in the body and preventing pathogens and foreign substances from entering. The epidermis is subdivided into additional layers that include, beginning with the outermost layer and extending deeper into the skin, the stratum corneum, stratum granulosum, stratum lucidum, stratum spinosum, and stratum basale. The epidermis contains no blood vessels and cells in the deepest layers of the epidermis are nourished by diffusion from blood capillaries extending to the upper layers of the dermis.
The epidermis and the dermis are separated by a thin sheet of fibers called the basement membrane which controls the traffic of cells and molecules between the dermis and the epidermis but also serves, through the binding of a variety of cytokins and growth factors, as a reservoir for their controlled release during physiological remodeling or repair processes. The dermis includes many nerve endings and it also contains the hair follicles, sweat glands, sebaceous glands, lymphatic vessels and blood vessels which provide nourishment and waste removal from its own cells as well as for the epidermis. The top area of the dermis adjacent to the epidermis is called the papillary region and the deeper area is known as the reticular region. The papillary region includes papillae or fingerlike projections that extend toward the epidermis and interdigitates with the epidermis strengthening the connection between the two layers of skin. The reticular region lies deeper and includes collagenous, elastic and reticular fibers that provide strength and elasticity. Also located within the reticular region are the roots of the hair and sweat glands and blood vessels. Beneath the dermis is the subcutaneous fat layer.
Penetration of the outer layers of skin to deliver a pharmaceutical composition is a widely held practice. FIG. 2 illustrates the penetration depths to reach certain layers of the skin. Approximately 0.25 mm penetrates the stratum corneum, approximately 0.5 mm from the outer surface reaches the middle of the epidermis, approximately 1.0 mm to approximately 2.0 mm reaches the basal layer; and approximately 2.5 mm penetrates the top of the dermis layer. In some applications, the bioavailability of an active ingredient may be increased with increased depth of penetration of the microneedles and hence, depth of delivery of the active ingredient.
Typically, injections of pharmaceuticals are achieved by subcutaneous delivery, intramuscular delivery, as well as intravenous delivery. Less invasive procedures have been developed and are also widely utilized. Among these less invasive procedures include topical applications such as patches, which are used to provide slow release of a composition. However, these patch delivery systems rely on formulations that can carry the active ingredients across the skin barrier into the blood stream. Therefore, there is a need for an article of manufacture that can be used to deliver a composition cutaneously or subcutaneously to the skin in a controlled and a convenient way that could be used by professionals or lay users. Specifically, there is also a need for an article that is capable of lancing the surface of skin or is capable of penetrating the surface of skin to a desired depth where a composition can be efficaciously applied.
One solution is the use of microneedles in which each individual microneedle is designed to puncture the skin up to a predetermined distance, which typically is desired to be greater than the nominal thickness of the stratum corneum layer of skin (the very outer layer of the skin out-covering the epidermis). Using such microneedles provides a great benefit in that the barrier properties of the skin are largely overcome. At the same time, the microneedles are relatively painless and bloodless if they are made to not penetrate through the epidermis, which is approximately less than 2.0-2.5 mm beneath the outer surface of the skin.
Microneedles require a direct pushing motion against the skin of sufficient force to penetrate completely through the stratum corneum. Furthermore, when the stratum corneum is penetrated, it is important to efficiently compel a matrix such as a liquid drug or other active ingredient though the relatively tiny openings created by the microneedles as the microneedles are usually quite small in diameter.
In general, microneedle stimulation systems are well known for their use in skin care treatment of various conditions such as wrinkles, acne scarring, stretch marks, skin whitening and facial rejuvenation. In microneedling, a method of piercing holes in the skin and applying drugs or cosmetics to the skin provides a way to rapidly and sufficiently permeate the skin. Another advantage of using microneedles is to injure the skin just enough to begin natural healing processes and stimulate collagen and elastin production, and the like, to heal the skin. In these methods, hundreds to thousands of tiny holes or microconduits are created in the skin with the microneedling device without damaging the deeper layers of the skin. This injury to the skin begins a natural healing process that leads to the release of natural stimulants and growth factors which stimulates the formation of new natural collagen and elastin in the papillary dermis to produce new, healthy skin tissue. Also, new capillaries are formed. This neovascularisation and neocollagenesis associated with the wound healing process leads to the formation of younger looking skin, reduction of skin pathologies and improvement of scars. Generally called percutaneous collagen induction therapy, microneedling has also been used in the treatment of photo ageing. Furthermore, medical substances may be applied to the site where the holes are created and the substances are supposed to permeate into the skin through the tiny holes. Microneedling is generally applied to the face, neck, scalp, and just about anywhere on the body where a particular condition warrants without removing or permanently damaging the skin. Microneedling is simple and safe. A predetermined number of needles are inserted into the skin to the desired depth. As a reaction to the minor injury, the skin tissue begins a natural wound-healing cascade. This natural process forms new healthy dermal tissue that helps smooth scars, remove wrinkles and improve pigmentation, and yields a younger, healthier and a cleaner-looking skin.
There is a need for an improved microneedling system. The present invention provides an improved microneedle roller system for mechanically perforating the outer skin layer in the presence of one or more active agents in a controlled environment that allows for approximation and absorption of the active compounds in a stable delivery environment. It is an object of the present invention to provide an improved microneedle mechanical delivery system that can provide a greater efficiency of flow from the device for one or more types of compounds topically and/or through the stratum corneum, and to the have the delivery system penetrate and stimulate the outer skin layers by a rolling motion across the skin at the same time.